Effective chemotherapy for advanced CNS embryonal tumors in adults.

PURPOSE: Embryonal tumors of the CNS include, among others, medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors (PNETs). Almost all data on the treatment of embryonal CNS tumors are derived from the pediatric population, since these tumors are uncommon in adulthood. The purpose of this study was to examine the rate and duration of response to chemotherapy of advanced embryonal CNS tumors in adults. PATIENTS AND METHODS: We retrospectively studied all adult (> 18 years of age) patients with advanced embryonal tumors of the CNS who received chemotherapy at our institution between 1976 and 1994. Seventeen consecutive patients were treated with regimens that contained either nitrosourea or cisplatin or both sequentially, with no patients having received the combination of nitrosourea and cisplatin concurrently. RESULTS: In patients who received cisplatin-based chemotherapy, responses were observed in 84.5% (26% complete response [CR] rate), 10.5% remained stable, and 5% progressed. The median time to progression was 18 months for patients who had a CR, 6 months for those with partial response (PR), and 10 months for stable patients. Among patients who received nitrosourea-based chemotherapy, PR was observed in 27%, 36.5% remained stable, and 36.5% progress. The median time to progression was 6 months for patients who had a PR and 6.5 months for stable patients. CONCLUSION: In adults with advanced embryonal CNS tumors, conventional-dose intravenous cisplatin-based chemotherapy regimens are able to produce responses in the majority of the patients (84.5%), even as second- or third-line regimens. Nitrosourea-based regimens less frequently produce responses (27%).

The neurologic complications of B-cell chronic lymphocytic leukemia.

We performed a retrospective study to characterize the type, frequency, and timing of neurologic complications in patients with B-cell chronic lymphocytic leukemia (B-CLL). We reviewed 962 total charts with a median follow-up time of 57.5 months. There were 109 cases (11.3%) of neurologic complications, including 69 cases (7.2%) of herpes zoster infection, 17 cases (1.8%) of other opportunistic infection, 14 cases (1.5%) of treatment-related conditions, eight cases (0.8%) of direct leukemic involvement of neural tissue, and 1 case (0.1%) of intracranial hemorrhage. No cases of a non-zoster opportunistic infection presented in early-stage (Rai stage 0-2) B-CLL, and only one case of direct leukemic involvement of neural structures presented in early-stage B-CLL. Of the 25 cases of non-zoster or treatment-related complications, only 5 presented before 6 years from the initial B-CLL diagnosis. Three of these were in advanced-stage B-CLL, staging could not be determined in one, and one presented in early-stage B-CLL. We conclude that the overall neurologic complication rate of B-CLL is low, and that the Rai stage of the disease correlates best with the risk of developing neurologic complications. The occurrence of a related non-zoster neurologic complication in a patient with B-CLL stage 0-2 approaches 1:1,000.

Use of orally administered opioids for cancer-related pain.

OBJECTIVE: To summarize the important principles of opioid analgesia for cancer-related pain. DESIGN: We reviewed our personal experience and reports in the literature to characterize commonly prescribed high-potency opioids and their relative efficacy. MATERIAL AND METHODS: The pharmacologic features of various opioids, selection of appropriate agents, titration of doses, routes of administration, conversions between drugs, and management of side effects are discussed. RESULTS: In general, the oral route is preferred because of ease of administration and good oral bioavailability of most opioids. In addition to the scheduled dosage of an opioid, extra "rescue" doses (5 to 10% of the total daily opioid dosage) should be available to the patient for breakthrough pain. Morphine is the prototype strong opioid against which other drugs are compared. Common adverse effects of opioids are sedation, nausea, constipation, respiratory depression, and myoclonus. Although no "standard" dose of opioid exists, the goals are to achieve adequate control of pain and to avoid major, unmanageable toxic effects. CONCLUSION: Pain is commonly associated with all stages of malignant disease. Despite its widespread occurrence, cancer pain is often inadequately managed because of poor assessment of pain and physicians' misconceptions about use of opioids. The cause of the pain should be carefully sought because it may yield important information about the underlying malignant disease. In most patients with moderate to severe cancer-related pain, oral administration of the appropriate opioid will achieve effective analgesia.

Paraneoplastic cerebellar degeneration: a clinical comparison of patients with and without Purkinje cell cytoplasmic antibodies.

In a review of 32 patients with paraneoplastic cerebellar degeneration (PCD), 16 (all of whom were women) had Purkinje cell cytoplasmic antibodies (PCAb) and 16 (8 women) did not. Most patients (15 of 16 seropositive and 12 of 16 seronegative patients) had active cancer at the time of neurologic diagnosis. Gynecologic or breast cancers were found in 14 of 16 seropositive and in 2 of 8 seronegative female patients; lung cancer was diagnosed in 7 of 16 seronegative patients but in no seropositive patient. In seropositive patients, the onset of the syndrome was more often abrupt and abnormalities of affect, mentation, ocular motility, and cerebrospinal fluid IgG index were more common than in seronegative patients. Additional paraneoplastic neurologic syndromes were present in five seronegative patients but in no seropositive patient. Clinical impairment was equivalent in both groups; approximately 75% of patients were confined to a wheelchair or bed at last follow-up. Four of 16 seropositive patients died (4 to 18 months after onset of PCD), and 7 of 16 seronegative patients died (7 to 120 months after onset of PCD). Thus, PCAb seem to be a marker for a clinical subset of female patients with gynecologic or breast cancer. The high frequency of other autoimmune paraneoplastic syndromes in patients with seronegative PCD suggests that PCD in both seropositive and seronegative patients may have a common pathogenic basis that involves an as yet unidentified antineuronal autoimmune mechanism.

Transdermal fentanyl in the management of cancer pain in ambulatory patients: an open-label pilot study.

We performed an open-label pilot study to define analgesic efficacy, acceptability, and toxicity of transdermal fentanyl in an ambulatory population of patients with cancer pain. Our 7-day study included 35 patients, all of whom had failed a trial of an opioid analgesic conventionally used for moderate pain. Patients received either a 25 micrograms/hr or 50 micrograms/hr fentanyl transdermal patch depending on prior opioid dose. Pain was measured daily utilizing visual analogue (VAS) and categorical (CAT) scales. Hours of nighttime sleep, quality of life, toxicities, and use of rescue medication were also assessed. There was a 24%-29% reduction in mean VAS and CAT pain scores as compared with the baseline and a 25% increase in mean hours of nighttime sleep. Fifty-nine percent of those patients responding (46% of all study patients) were satisfied to very satisfied with the analgesia provided by transdermal fentanyl. Six percent of all study patients were not at all satisfied with the pain relief obtained. Toxicities were similar to those seen with other opioids. No patient developed severe sedation or respiratory depression. The 25-50 micrograms/hr patch appears to be a safe starting dosage in ambulatory patients previously receiving opioids conventionally used for moderate pain.

Primary central nervous system lymphoma presenting as autonomic dysfunction.

We describe a patient with primary central nervous system lymphoma (PCNSL) who presented with symptoms of subacute onset of dysautonomia. Autonomic testing indicated a peripheral autonomic neuropathy while magnetic resonance imaging revealed brainstem involvement. We propose that this patient's autonomic dysfunction could be the result of a paraneoplastic syndrome and PCNSL should be considered in the differential diagnosis of dysautonomia.

Chronic lymphocytic leukaemia with symptomatic diffuse central nervous system infiltration responding to therapy with systemic fludarabine.

B-cell chronic lymphocytic leukaemia is an indolent disease characterized by the insidious accumulation of small mature-appearing lymphocytes in the peripheral blood, bone marrow and lymphoid tissues. Direct symptomatic invasion of the central nervous system is exceedingly rare and, to our knowledge, only three cases histologically confirmed as true chronic lymphocytic leukaemia have been reported in the literature. We describe the first case of early Rai stage B-cell chronic lymphocytic leukaemia presenting with symptomatic infiltration of the brain and spinal cord which could be demonstrated radiographically by magnetic resonance imaging. The diagnosis was confirmed by examination of peripheral blood, cerebrospinal fluid, brain and bone marrow biopsies, both morphologically and immunophenotypically by means of flow cytometric analysis. The patient demonstrated a complete response to therapy with standard-dose systemic fludarabine and remains in complete remission 6 months after completion of therapy.